Everything in Moderation… Including Pain

Finding new ways to understand how our pain pathways work is vital to increasing the quality of life for people with chronic conditions.

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If you ask biologist David Julius, the most important sensory system to a person’s survival is the ability to sense pain and touch. It might not have been the first sense to pop into your mind, but it has huge importance for life expectancy. Without it, injuries are much more likely, and they could even go unnoticed.

Julius, professor of physiology at the University of California San Francisco and 2017 Canada Gairdner International Award Laureate, determined the molecular basis for how we sense heat, cold, and pain, and how those signals are transmitted from the body to the brain.

Normal pain pathways serve as a warning system that allows people to avoid injury, but when they become too sensitive, people can experience chronic pain.

“People who have chronic pain syndromes, their lives can get really turned upside down,” says Julius. “They can become immobile. They might take a panoply of drugs that make them unable to drive, or decrease their function. They can become socially isolated, stop being active. Persistent chronic pain can be quite debilitating.”

With recent advances in medical imaging, Julius believes even more opportunities are now open to understand pain signals and pain perception.

“There’s a lot known now about how we detect different types of stimuli at the periphery, like at our fingertips,” says Julius. “The question is, how are those signals sent into the central nervous system, like our spinal cord and brain, and how is all that information integrated?”

Researchers will be better equipped to probe the routes that those signals take, and how the brain sorts the information to generate the perception of pain.

Julius also hopes that progress will be made in developing new and more selective drugs to target specific types of pain.

“Pain is not really just one disease: it’s like cancer. You know, it should be called ‘pains’, because there’s many different types of pain, and I think that we need more options to treat those different types of pain, because they’ll respond to different types of therapies.”

Painkillers like opiates work on a broad spectrum of pain, but they can be addictive and deadly, lending urgency to the quest for new ways to target pain pathways.

Understanding this vital sense that gives us better survival instincts could go a long way toward comforting patients with injuries or disease when the signal gets too loud.

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David Julius has used distinctive molecules from the natural world – including toxins from tarantulas and coral snakes – to understand how signals responsible for temperature and pain sensation are transmitted by neural circuits to the brain. In his research, Julius homed in on a class of proteins called TRP (pronounced “trip”) ion channels to discover how capsaicin, the chemical compound responsible for the spicy heat of chili peppers, elicits a burning sensation when eaten or touched. The research led to the identification and cloning of the specific protein responsible, named TRPV1. On the flip side, Julius has used menthol, a natural cooling agent, to identify a receptor for “real” cold. This protein, named TRPM8, is a close molecular cousin of TRPV1, pointing to a common mechanism for sensing temperature. As in the case of TRPV1, this ion channel contributes to hypersensitivity to cold, such as that experienced after chemotherapy or other types of nerve injury. Somatosensation, our sense of touch and pain, serves as a warning system to guard us against injury. While critical to our survival and well-being, this system can become hypersensitive, resulting in chronic pain. This work helps to explain how such positive and negative aspects of pain sensation arise – insight that is critical to understanding the genesis of chronic pain syndromes. One indication of the importance of this work to medicine is the interest in TRP channels as potential targets for a new generation of painkillers.

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